Accelerating antiviral drug discovery: early hazard detection with a dual zebrafish and cell culture screen of a 403 compound library.

The constant emergence of new viral pathogens underscores the need for continually evolving, effective antiviral drugs. A key challenge is identifying compounds that are both efficacious and safe, as many candidates fail during development due to unforeseen toxicity. To address this, the embryonic zebrafish morphology, mortality, and behavior (ZBE) screen and the SYSTEMETRIC® Cell Health Screen (CHS) were employed to evaluate the safety of 403 compounds from the Cayman Antiviral Screening Library.

Identifying antibiotic-resistant strains via cell sorting and elastic-light-scatter phenotyping.

The proliferation and dissemination of antimicrobial-resistant bacteria is an increasingly global challenge and is attributed mainly to the excessive or improper use of antibiotics. Currently, the gold-standard phenotypic methodology for detecting resistant strains is agar plating, which is a time-consuming process that involves multiple subculturing steps. Genotypic analysis techniques are fast, but they require pure starting samples and cannot differentiate between viable and non-viable organisms.

Spectral flow cytometry: Fundamentals and future impact.

Spectral flow cytometry has emerged as a significant player in the cytometry marketplace, with the potential for rapid growth. Despite a slow start, the technology has made significant strides in advancing various areas of single-cell analysis utilized by the scientific community. The integration of spectral cytometry into clinical laboratories and diagnostic processes is currently underway and is expected to garner a significant level of widespread acceptance in the near future.

Identification of predictive patient characteristics for assessing the probability of COVID-19 in-hospital mortality.

As the world emerges from the COVID-19 pandemic, there is an urgent need to understand patient factors that may be used to predict the occurrence of severe cases and patient mortality. Approximately 20% of SARS-CoV-2 infections lead to acute respiratory distress syndrome caused by the harmful actions of inflammatory mediators. Patients with severe COVID-19 are often afflicted with neurologic symptoms, and individuals with pre-existing neurodegenerative disease have an increased risk of severe COVID-19.

A versatile information retrieval framework for evaluating profile strength and similarity.

In profiling assays, thousands of biological properties are measured in a single test, yielding biological discoveries by capturing the state of a cell population, often at the single-cell level. However, for profiling datasets, it has been challenging to evaluate the phenotypic activity of a sample and the phenotypic consistency among samples, due to profiles' high dimensionality, heterogeneous nature, and non-linear properties. Existing methods leave researchers uncertain where to draw boundaries between meaningful biological response and technical noise.

Hybrid Raman and Laser-Induced Breakdown Spectroscopy for Food Authentication Applications.

The issue of food fraud has become a significant global concern as it affects both the quality and safety of food products, ultimately resulting in the loss of customer trust and brand loyalty. To address this problem, we have developed an innovative approach that can tackle various types of food fraud, including adulteration, substitution, and dilution. Our methodology utilizes an integrated system that combines laser-induced breakdown spectroscopy (LIBS) and Raman spectroscopy.

Comparative analysis between zebrafish and an automated live-cell assay to classify developmental neurotoxicant chemicals.

Modern toxicology's throughput has dramatically increased due to alternative models, laboratory automation, and machine learning. This has enabled comparative studies across species and assays to prioritize chemical hazard potential and to understand how different model systems might complement one another. However, such comparative studies of high-throughput data are still in their infancy, with more groundwork needed to firmly establish the approach.

Flow Cytometry: The Next Revolution.

Unmasking the subtleties of the immune system requires both a comprehensive knowledge base and the ability to interrogate that system with intimate sensitivity. That task, to a considerable extent, has been handled by an iterative expansion in flow cytometry methods, both in technological capability and also in accompanying advances in informatics. As the field of fluorescence-based cytomics matured, it reached a technological barrier at around 30 parameter analyses, which stalled the field until spectral flow cytometry created a fundamental transformation that will likely lead to the potential of 100 simultaneous parameter analyses within a few years.

Bacterial Colony Phenotyping with Hyperspectral Elastic Light Scattering Patterns.

The elastic light-scatter (ELS) technique, which detects and discriminates microbial organisms based on the light-scatter pattern of their colonies, has demonstrated excellent classification accuracy in pathogen screening tasks. The implementation of the multispectral approach has brought further advantages and motivated the design and validation of a hyperspectral elastic light-scatter phenotyping instrument (HESPI). The newly developed instrument consists of a supercontinuum (SC) laser and an acousto-optic tunable filter (AOTF).

A novel statistical methodology for quantifying the spatial arrangements of axons in peripheral nerves.

A thorough understanding of the neuroanatomy of peripheral nerves is required for a better insight into their function and the development of neuromodulation tools and strategies. In biophysical modeling, it is commonly assumed that the complex spatial arrangement of myelinated and unmyelinated axons in peripheral nerves is random, however, in reality the axonal organization is inhomogeneous and anisotropic. Present quantitative neuroanatomy methods analyze peripheral nerves in terms of the number of axons and the morphometric characteristics of the axons, such as area and diameter.

Surface Environment and Energy Density Effects on the Detection and Disinfection of Microorganisms Using a Portable Instrument.

Real-time detection and disinfection of foodborne pathogens are important for preventing foodborne outbreaks and for maintaining a safe environment for consumers. There are numerous methods for the disinfection of hazardous organisms, including heat treatment, chemical reaction, filtration, and irradiation. This report evaluated a portable instrument to validate its simultaneous detection and disinfection capability in typical laboratory situations.

Rapid Food Authentication Using a Portable Laser-Induced Breakdown Spectroscopy System.

Laser-induced breakdown spectroscopy (LIBS) is an atomic-emission spectroscopy technique that employs a focused laser beam to produce microplasma. Although LIBS was designed for applications in the field of materials science, it has lately been proposed as a method for the compositional analysis of agricultural goods. We deployed commercial handheld LIBS equipment to illustrate the performance of this promising optical technology in the context of food authentication, as the growing incidence of food fraud necessitates the development of novel portable methods for detection.

Impact of combination of short lecture and group discussion on the learning of physiology by nonmajor undergraduates.

This study assessed the impact of an "active learning" strategy employed alone or in combination with traditional lectures on the learning of mammalian physiology by undergraduate students. The study investigated the impact of three teaching strategies, namely ) traditional lecture, ) group discussion alone, and ) combination of lecture and group discussion. For all strategies, students were given homework in a textbook and they completed written assignments before each session.

Development of a Smartphone-Integrated Reflective Scatterometer for Bacterial Identification.

We present a smartphone-based bacterial colony phenotyping instrument using a reflective elastic light scattering (ELS) pattern and the resolving power of the new instrument. The reflectance-type device can acquire ELS patterns of colonies on highly opaque media as well as optically dense colonies. The novel instrument was built using a smartphone interface and a 532 nm diode laser, and these essential optical components made it a cost-effective and portable device.

A Semi-Automated Method for Measuring Biofilm Accumulation on the Teeth Using Quantitative Light-Induced Fluorescence in Dogs and Cats.

Oral health conditions (eg, plaque, calculus, gingivitis) cause morbidity and pain in companion animals. Thus, developing technologies that can ameliorate the accumulation of oral biofilm, a critical factor in the progression of these conditions, is vital. Quantitative light-induced fluorescence (QLF) is a method to quantify oral substrate accumulation, and therefore, it can assess biofilm attenuation of different products.

High-throughput segmentation of unmyelinated axons by deep learning.

Axonal characterizations of connectomes in healthy and disease phenotypes are surprisingly incomplete and biased because unmyelinated axons, the most prevalent type of fibers in the nervous system, have largely been ignored as their quantitative assessment quickly becomes unmanageable as the number of axons increases. Herein, we introduce the first prototype of a high-throughput processing pipeline for automated segmentation of unmyelinated fibers. Our team has used transmission electron microscopy images of vagus and pelvic nerves in rats.

Local and Systemic Changes in Lipid Profile as Potential Biomarkers for Canine Atopic Dermatitis.

Lipids play a critical role in the skin as components of the epidermal barrier and as signaling and antimicrobial molecules. Atopic dermatitis in dogs is associated with changes in the lipid composition of the skin, but whether these precede or follow the onset of dermatitis is unclear. We applied rapid lipid-profiling mass spectrometry to skin and blood of 30 control and 30 atopic dogs.

Unique Neural Circuit Connectivity of Mouse Proximal, Middle, and Distal Colon Defines Regional Colonic Motor Patterns.

Background & Aims: Colonic motor patterns have been described by a number of different groups, but the neural connectivity and ganglion architecture supporting patterned motor activity have not been elucidated. Our goals were to describe quantitatively, by region, the structural architecture of the mouse enteric nervous system and use functional calcium imaging, pharmacology, and electrical stimulation to show regional underpinnings of different motor patterns.

Methods: Excised colon segments from mice expressing the calcium indicator GCaMP6f or GCaMP6s were used to examine spontaneous and evoked (pharmacologic or electrical) changes in GCaMP-mediated fluorescence and coupled with assessment of colonic motor activity, immunohistochemistry, and confocal imaging.

Acute cell stress screen with supervised machine learning predicts cytotoxicity of excipients.

Excipients serve as vehicles, preservatives, solubilizers, and colorants for drugs, food, and cosmetics. They are considered to be inert at biological targets; however, several reports suggest that some could interact with human targets and cause unwanted effects. We investigated 40 commonly used drug excipients for cellular stress in the AsedaSciences® SYSTEMETRIC® Cell Health Screen, which was developed to estimate toxicity risk of small molecular entities (SMEs).

Optical multi-channel interrogation instrument for bacterial colony characterization.

A single instrument that includes multiple optical channels was developed to simultaneously measure various optical and associated biophysical characteristics of a bacterial colony. The multi-channel device can provide five distinct optical features without the need to transfer the sample to multiple locations or instruments. The available measurement channels are bright-field light microscopy, 3-D colony-morphology map, 2-D spatial optical-density distribution, spectral forward-scattering pattern, and spectral optical density.

Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion.

Epidemiological studies have identified a correlation between maternal helminth infections and reduced immunity to some early childhood vaccinations, but the cellular basis for this is poorly understood. Here, we investigated the effects of maternal Schistosoma mansoni infection on steady-state offspring immunity, as well as immunity induced by a commercial tetanus/diphtheria vaccine using a dual IL-4 reporter mouse model of maternal schistosomiasis. We demonstrate that offspring born to S.

Stomach region stimulated determines effects on duodenal motility in rats.

Gastric electrical stimulation (GES) is used clinically to promote proximal GI emptying and motility. In acute experiments, we measured duodenal motor responses elicited by GES applied at 141 randomly chosen electrode sites on the stomach serosal surface. Overnight-fasted (HO available) anesthetized male rats ( = 81) received intermittent biphasic GES for 5 min (20-s-on/40-s-off cycles; I = 0.

A novel experimental workflow to determine the impact of storage parameters on the mass spectrometric profiling and assessment of representative phosphatidylethanolamine lipids in mouse tissues.

Evaluation of signaling lipids is essential for measuring biological processes. There is a lack of experimental data regarding the proper storage of extracts for signaling lipid analysis, potentially impacting the procedures that can lead to accurate and reproducible evaluation. In this study, the importance of pre-analytical conditions for analyzing ion transitions for phosphatidylethanolamines (PEs), an abundant signaling phospholipid, was systematically assessed.

Lipidomic Profiling of the Epidermis in a Mouse Model of Dermatitis Reveals Sexual Dimorphism and Changes in Lipid Composition before the Onset of Clinical Disease.

Atopic dermatitis (AD) is a multifactorial disease associated with alterations in lipid composition and organization in the epidermis. Multiple variants of AD exist with different outcomes in response to therapies. The evaluation of disease progression and response to treatment are observational assessments with poor inter-observer agreement highlighting the need for molecular markers.

An emerging method to noninvasively measure and identify vagal response markers to enable bioelectronic control of gastroparesis symptoms with gastric electrical stimulation.

Background: Gastric electrical stimulation (GES) can be a life-changing, device-based treatment option for drug-resistant nausea and vomiting associated with diabetic or idiopathic gastroparesis (GP). Despite over two decades of clinical use, the mechanism of action remains unclear. We hypothesize a vagal mechanism.